Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

Abstract

Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug-and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.

Hydrogen-Bond-Driven Core-Crosslinked Supramolecular Micelles with pH/Thermal/Glutathione-Responsive Drug Release toward Enhanced Cancer Therapy

“…1,2 Tailor-made polymeric biomaterials 3,4 are paving the way for medical treatment and healthcare strategies due to their broad impact on both structural and functional flexibility. 5−8 Noncovalent interactions 9 such as H-bond, 10,11 host−guest interaction, 12,13 metal−ligand coordination 14−16 can be integrated into polymeric biomaterials (e.g., cancer nanomedicine), whose properties follow from the dynamic and intelligent nature of their constituents. 17 Clear advantages of such a strategy include the molecular-level recognition of targets, superior efficiency for incorporating drugs, and a novel technique to construct a delivery platform responsive to specific physiologic indicators.…”

“…Despite the growing investigations and remarkable advances in H-bonded nanomedicine, there is still a long way to go. 11 Promoted drug loading content, high stability in physiological fluid, responsive charge reversal, and smart drug release are the persistent goals we strive for. With these aims in mind, in this work, α,ω-functionalized symmetrical H-bonding prodrug (FUS) linked via disulfide bonds is firstly targeted, bearing FU motifs at both chain ends (Figure 1a).…”

“…Noncovalent interactions such as H-bond, , host–guest interaction, , metal–ligand coordination − can be integrated into polymeric biomaterials ( e.g. , cancer nanomedicine), whose properties follow from the dynamic and intelligent nature of their constituents .…”

“…Chemotherapeutic drugs bearing an inherent H-bonding array reflect a particular structure merit, which can thus contribute to the principle of designing novel H-bonded supramolecular nanomedicine. Drugs bonded within the nano-assemblies through H-bonding forces collectively with hydrophobic interactions exhibit promoted drug loading content and enhanced stability . In addition, stimulus-responsive and controlled drug release, sensitive to diverse parameters such as temperature, , pH, − or radiation, can be readily achieved on account of the dynamic characteristics of H-bonding interaction, improving the antitumor efficiency and reducing the toxic side effects.…”

“…Despite the growing investigations and remarkable advances in H-bonded nanomedicine, there is still a long way to go . Promoted drug loading content, high stability in physiological fluid, responsive charge reversal, and smart drug release are the persistent goals we strive for.…”